Type II Hypersensitivities: Videos & Practice Problems

Type II hypersensitivities involve IgG or IgM antibodies targeting cell surface antigens, causing cytotoxic effects like hemolytic transfusion reactions and hemolytic disease of the newborn (HDNB). The ABO and Rh blood group systems determine transfusion compatibility, where mismatched antigens trigger antibody-dependent cell-mediated cytotoxicity, leading to red blood cell lysis. Proper transfusions follow donate and receive rules based on antigen presence. HDNB arises when an Rh-negative mother is sensitized to Rh-positive fetal antigens, preventable by RhoGAM, which blocks maternal immune sensitization, highlighting the importance of adaptive immunity and complement activation in transfusion medicine.

Type II Hypersensitivity

Type II hypersensitivities, also known as cytotoxic hypersensitivities, involve immune responses mediated primarily by IgG and IgM antibodies. Unlike Type I hypersensitivities, which are driven by IgE antibodies, Type II hypersensitivities target antigens located directly on cell surfaces or within the extracellular matrix. These antigens can be foreign, such as donor red blood cells in a transfusion, or self-antigens, leading to autoimmune disorders. The hallmark of most Type II hypersensitivities is cell death, which occurs through mechanisms like cytolysis, antibody-dependent cellular cytotoxicity (ADCC), or inflammation-induced tissue damage.

In cytotoxic Type II hypersensitivities, antibodies bind to cell-bound antigens, triggering cell death via two main pathways. The complement-dependent pathway activates the complement system, leading to cell lysis and inflammation, while the complement-independent pathway recruits natural killer cells to induce cell death without complement activation. Both pathways culminate in tissue damage, which is a detrimental consequence of these immune reactions.

Common examples of cytotoxic Type II hypersensitivities include hemolytic transfusion reactions, where incompatible blood transfusions cause destruction of foreign red blood cells, and hemolytic disease of the newborn, where maternal antibodies attack fetal red blood cells. Autoimmune hemolytic anemia is an example where the immune system mistakenly targets the body’s own red blood cells, illustrating how self-cells can also be affected.

Not all Type II hypersensitivities are cytotoxic, however. Non-cytotoxic Type II hypersensitivities exclusively target self-cells and result in autoimmune disorders by altering receptor function rather than causing cell death. In these cases, IgG antibodies bind to receptors on self-cells, either inactivating or overstimulating them. This abnormal receptor modulation disrupts normal cellular responses, affecting systems such as the endocrine or musculoskeletal systems.

For instance, myasthenia gravis is a non-cytotoxic Type II hypersensitivity where antibodies inactivate acetylcholine receptors on muscle cells, leading to muscle weakness and fatigue. Conversely, Graves’ disease involves antibodies that overstimulate thyroid hormone receptors, causing excessive thyroid hormone production and associated symptoms.

Overall, Type II hypersensitivities demonstrate how antibodies can mistakenly target either foreign or self-antigens, leading to harmful effects through cell destruction or receptor dysfunction. Understanding these mechanisms is crucial for diagnosing and managing conditions like hemolytic transfusion reactions, autoimmune hemolytic anemia, myasthenia gravis, and Graves’ disease.

Which of the following is not a way that type II hypersensitivity can cause tissue damage?

• A. Cell lysis.
• B. Phagocytosis.
• C. Degranulation of basophils & release of proinflammatory mediators.
• D. Overstimulation of receptors.

Answer: (C)

Understanding the ABO Blood System

The ABO blood system is a fundamental classification of human blood based on the presence or absence of specific carbohydrate antigens on the surface of red blood cells. There are four primary blood types: Type A, Type B, Type AB, and Type O. Type A blood has A antigens on the red blood cells, Type B has B antigens, Type AB has both A and B antigens, while Type O lacks both A and B antigens.

In addition to these antigens, the plasma contains antibodies known as isohemagglutinins or isoantibodies, which are naturally produced against the ABO antigens that the individual’s red blood cells do not possess. For example, a person with Type A blood, which lacks B antigens, produces anti-B antibodies. Conversely, Type B blood produces anti-A antibodies. Type AB blood, having both antigens, does not produce anti-A or anti-B antibodies, while Type O blood, lacking both antigens, produces both anti-A and anti-B antibodies.

This immune response is critical in blood transfusions because incompatible transfusions can trigger the recipient’s antibodies to attack the donor’s red blood cells, causing agglutination (clumping) and hemolysis (destruction of red blood cells). Such reactions can be life-threatening, highlighting the importance of matching blood types correctly during transfusions.

It is also important to note that whole blood transfusions are rarely used. Instead, blood components are separated, and typically only red blood cells are transfused. This separation reduces the risk associated with donor plasma antibodies, making the compatibility between the donor’s red blood cell antigens and the recipient’s antibodies the primary concern for transfusion safety.

Understanding the ABO blood system and the role of antigens and antibodies is essential for safe blood transfusion practices and for preventing type two hypersensitivity reactions, such as hemolytic transfusion reactions.

Understanding the Rh Blood System

The Rh blood system is an essential component of blood typing that works alongside the ABO blood system. In addition to the A and B antigens found on red blood cells, the Rh system involves the presence or absence of the Rh factor, a protein antigen on the surface of red blood cells. Individuals who have the Rh factor are classified as Rh positive, which constitutes approximately 85% of the human population. Conversely, those who lack the Rh factor are Rh negative.

Blood types are thus categorized not only by the ABO system but also by the Rh factor, resulting in eight common blood types: A positive, B positive, AB positive, O positive, and their Rh negative counterparts—A negative, B negative, AB negative, and O negative. The Rh factor is typically represented as a distinct marker on red blood cells, indicating Rh positivity.

Unlike the naturally occurring anti-A and anti-B antibodies in the ABO system, anti-Rh antibodies are not normally present in Rh negative individuals. However, if an Rh negative person is exposed to Rh positive blood, their immune system may become sensitized and begin producing anti-Rh antibodies. This immune response is permanent and can lead to a hemolytic transfusion reaction if the individual later receives Rh positive blood. Therefore, Rh negative individuals should only receive Rh negative blood during transfusions to avoid this potentially dangerous reaction.

On the other hand, Rh positive individuals do not produce anti-Rh antibodies and can safely receive blood from both Rh positive and Rh negative donors. This distinction is crucial for ensuring compatibility in blood transfusions and preventing immune complications.

Understanding the interplay between the ABO and Rh blood systems is vital for safe blood transfusion practices. The combination of these systems defines the eight primary blood types, each with specific compatibility rules. This knowledge helps prevent adverse transfusion reactions and supports effective clinical decision-making in transfusion medicine.

Type II Hypersensitivities Example 1

The human ABO blood group system classifies blood into four major types: A, B, AB, and O, based on the presence or absence of specific antigens on the surface of red blood cells. Blood type is determined by the antigens present: type A has A antigens, type B has B antigens, type AB has both A and B antigens, and type O has neither A nor B antigens.

Antibodies in the plasma correspond to the antigens that are absent on the red blood cells. For example, a person with type O blood, which lacks both A and B antigens, naturally produces both anti-A and anti-B antibodies. This immune response prevents the body from reacting to foreign blood types during transfusions.

It is important to note that anti-O antibodies do not exist, as the O blood type is defined by the absence of A and B antigens rather than the presence of an O antigen. Additionally, individuals do not produce antibodies against their own antigens; for instance, a person with type B blood has B antigens on their red blood cells and therefore produces anti-A antibodies, not anti-B antibodies, to avoid attacking their own cells.

Understanding the relationship between blood type antigens and corresponding antibodies is crucial for safe blood transfusions and organ transplants. The ABO system exemplifies how the immune system recognizes self versus non-self, highlighting the importance of antigen-antibody compatibility in medical practice.

Which of the following statements about Rh factors is true?

• A. Rh factor and AB antigens cannot be found on the same red blood cell.
• B. An individual with Rh⁺ blood will make anti-Rh antibodies after exposure to Rh antigens.
• C. Rh factors are antigens found on the surface of red blood cells in individuals with a + blood type.
• D. Rh factors are lipid antigens found on the surface of red blood cells in individuals with a – blood type.

Answer: (C)

A patient’s blood type is AB—, therefore ___________.

• A. Their RBCs have no A or B antigens.
• B. Their RBCs have A antigens and the Rh factor.
• C. Their RBCs have A and B antigens and the Rh factor.
• D. Their RBCs have A & B antigens but not the Rh factor.

Answer: (D)

Proper Blood Transfusions Based on Blood Types

Understanding proper blood transfusions requires knowledge of the ABO and Rh blood group systems, which categorize blood into eight distinct types based on the presence or absence of A, B, and Rh antigens on red blood cells. Safe blood transfusions depend on preventing adverse reactions caused by the recipient's antibodies attacking donor red blood cell antigens. This safety is ensured by following two fundamental principles: the Donate Rule and the Receive Rule.

The Donate Rule states that a person can only donate blood to recipients whose red blood cells have at least the same antigens as the donor's, or more. For example, individuals with A positive blood have both A and Rh antigens on their red blood cells. Therefore, they can donate to recipients who have at least these two antigens, such as those with A positive or AB positive blood types. The presence of additional antigens, like the B antigen in AB positive blood, does not prevent donation as long as the recipient’s cells contain the donor’s antigens.

Conversely, the Receive Rule specifies that a person can only receive blood from donors whose red blood cells have at most the same antigens as the recipient’s, or fewer. Applying this to A positive blood, recipients can safely receive blood from A positive donors (same antigens), A negative donors (lacking Rh antigen), O positive donors (lacking A antigen), and O negative donors (lacking both A and Rh antigens). This means A positive individuals cannot receive blood containing the B antigen, as their antibodies would react against it.

These two rules are essentially inverse to each other, making it easier to remember one if the other is known. When applied to all eight blood types, these principles clarify compatibility for blood transfusions. Notably, AB positive blood is known as the universal recipient because it contains all three antigens—A, B, and Rh—allowing it to receive blood from any type without antibody reactions. However, AB positive individuals can only donate to others with the same blood type.

On the other hand, O negative blood is the universal donor type. It lacks A, B, and Rh antigens, so it can be safely transfused to recipients of any blood type without triggering an immune response. However, O negative individuals can only receive blood from other O negative donors, as their immune system would react to any antigens present in other blood types.

By understanding the interaction between red blood cell antigens and recipient antibodies, and applying the Donate and Receive Rules, one can confidently determine safe blood transfusion matches. This knowledge is crucial for preventing transfusion reactions and ensuring patient safety during blood transfusions.

A patient with type A⁺ blood is in the emergency room & requires a blood transfusion. Which of the following types of blood could they receive?


I) Type O⁺
II) Type A^–
III) Type B⁺
IV) Type AB^–

• A. I or II only.
• B. I or III only.
• C. II or IV only.
• D. I, II, or III.
• E. II, III or IV.
• F. I, II or IV.

Answer: (A)

Improper Blood Transfusion Reactions

Hemolytic transfusion reactions (HTRs) occur when incompatible donor red blood cells are destroyed by the recipient's immune system, representing a classic example of a cytotoxic type II hypersensitivity reaction. The term "hemolytic" combines "heme," meaning blood, and "lytic," meaning destruction or bursting of cells. During an HTR, the recipient's antibodies recognize and bind to antigens on the transfused red blood cells that are foreign, marking them for immune-mediated destruction.

For instance, if a patient with type B blood receives type A blood, their anti-A antibodies will target the donor's A antigens. This antibody-antigen interaction triggers the lysis of the donor red blood cells. While the immune system is effectively protecting the body by attacking foreign cells, this reaction can have severe consequences. The destruction of a large volume of red blood cells releases intracellular contents that can provoke inflammation, activate blood clotting pathways, and cause damage to the kidneys. In severe cases, this can lead to shock and failure of vital organs, making hemolytic transfusion reactions a medical emergency.

Understanding the immunological basis of HTRs highlights the critical importance of blood type compatibility in transfusions. The antibodies involved are specific to blood group antigens, such as anti-A or anti-B antibodies, which bind to their corresponding antigens on red blood cells. This binding initiates complement activation and cell lysis, emphasizing why matching donor and recipient blood types is essential to prevent these life-threatening reactions.

Why would someone with type O— blood be considered a “universal donor”?

• A. Type O^— RBCs do not have A or B antigens & therefore would not cause a transfusion reaction when donated.
• B. Type O^— blood does not contain any antibodies that bind to antigens on red blood cells. 
• C. Type O^— RBCs have antibodies that bind to both A & B antigens, so it integrates well with other blood types.
• D. Type O^— blood only has O antigens, which are not recognized as foreign by any human antibodies.

Answer: (A)

All the following statements about hemolytic transfusion reactions are true except:

• A. The patient’s IgM antibodies will recognize foreign red blood cells and tag those cells for destruction. 
• B. The patient’s antigens recognize antigens on donated RBCs, triggering a type II hypersensitivity reaction.
• C. To avoid these reactions, patients are given blood that is either the same type as their own or type O^— blood.
• D. If a patient who has type B blood is given donated type A blood, an HTR will occur in the patient.

Answer: (B)

What will happen if a patient is accidentally given blood that does not match their own AB or Rh antigens?

• A. Isohemagglutinins bind to the foreign red blood cells triggering the destruction of mast cells and basophils.
• B. The immune system will attack all foreign and “self” red blood cells, resulting in blood clots.
• C. Complement system proteins attack & destroy foreign red blood; cell membranes can cause blood clots & the released hemoglobin in the bloodstream can cause kidney damage.
• D. All of the above.

Answer: (C)

Hemolytic Disease of the Newborn (HDNB)

Hemolytic disease of the newborn (HDNB) is a serious condition caused by a cytotoxic type II hypersensitivity reaction. It occurs when an Rh-negative mother carries an Rh-positive fetus, leading to the mother's immune system becoming sensitized to Rh antigens. During pregnancy or more commonly at birth, Rh antigens from the fetus can enter the mother's bloodstream, triggering her immune system to produce anti-Rh IgG antibodies. These antibodies do not affect the first Rh-positive fetus but pose a risk in subsequent pregnancies with Rh-positive fetuses.

In subsequent pregnancies, the mother's anti-Rh IgG antibodies can cross the placenta and attack the red blood cells of the Rh-positive fetus. This immune response causes hemolysis, leading to anemia, heart failure, jaundice, brain damage, and potentially death in the fetus. The disease specifically targets Rh-positive fetuses and newborns, while Rh-negative fetuses remain unaffected. Importantly, the mother herself does not suffer harm from HDNB; the condition exclusively impacts the fetus.

The development of HDNB can be understood in three phases. The first phase involves exposure to Rh antigens, typically occurring late in the first pregnancy or during delivery, when fetal red blood cells enter the maternal circulation. The second phase is sensitization, where the mother's immune system produces anti-Rh IgG antibodies in response to these antigens. The third phase occurs in subsequent pregnancies, where these antibodies cross the placenta and destroy fetal red blood cells, causing hemolytic disease.

Understanding the immunological mechanism behind HDNB highlights the importance of Rh compatibility in pregnancy. The anti-Rh IgG antibodies are central to the pathology, as their ability to cross the placenta and target fetal erythrocytes leads to the clinical manifestations of the disease. This knowledge is crucial for anticipating risks in Rh-negative mothers carrying Rh-positive fetuses and underscores the need for preventive and therapeutic strategies to protect fetal health.

Treating HDNB

Hemolytic disease of the newborn (HDNB) is a condition that can be effectively prevented through the strategic administration of anti-Rh antibody medication, such as RhoGAM. Although it may seem counterintuitive, these anti-Rh antibodies are used to prevent, rather than cause, HDNB. The key lies in the precise dosage: enough to inhibit the mother's immune system from becoming sensitized to Rh-positive fetal red blood cells, but not enough to harm the fetus.

When an Rh-negative mother carries an Rh-positive fetus, fetal red blood cells expressing Rh antigens can enter the mother's bloodstream, especially during childbirth. Without intervention, this exposure can sensitize the mother's immune system, prompting it to produce anti-Rh IgG antibodies. These antibodies can cross the placenta in subsequent pregnancies and attack the red blood cells of an Rh-positive fetus, leading to HDNB.

RhoGAM contains anti-Rh antibodies that bind to the Rh antigens on fetal red blood cells before the mother's immune system recognizes them. This binding prevents the mother's immune system from becoming sensitized and producing its own anti-Rh antibodies. Since sensitization is permanent and irreversible, administering RhoGAM during and after the first pregnancy with an Rh-positive fetus is crucial to prevent HDNB in future pregnancies.

In summary, preventing the mother's immune sensitization to Rh antigens is essential to avoid hemolytic disease of the newborn. The use of anti-Rh antibody medication like RhoGAM effectively blocks this sensitization, safeguarding Rh-positive fetuses in subsequent pregnancies from immune-mediated hemolysis.

Type II Hypersensitivities Example 3

Hemolytic disease of the newborn (HDNB) occurs when an Rh-negative mother becomes sensitized to Rh-positive fetal blood cells, leading to the production of anti-Rh antibodies that can attack the red blood cells of subsequent Rh-positive infants. The key factor in HDNB is the mother's immune system exposure to Rh antigens, which typically happens during or after the birth of an Rh-positive baby.

In the case of an Rh-negative mother's firstborn with Rh-positive blood, the infant is usually not affected by HDNB because the mother's immune system is only exposed to the Rh antigen late in pregnancy or during delivery. This exposure sensitizes the mother but does not produce antibodies in time to harm the firstborn. Therefore, the firstborn with Rh-positive blood is generally not at risk.

Conversely, if the mother is Rh-positive, her immune system is naturally tolerant to Rh antigens and does not produce anti-Rh antibodies. Thus, infants born to Rh-positive mothers, regardless of their Rh status, are not at risk for HDNB.

The highest risk for HDNB occurs with an Rh-negative mother's second baby who has Rh-positive blood, provided the first baby was also Rh-positive. In this scenario, the first Rh-positive baby sensitizes the mother's immune system, causing it to produce anti-Rh antibodies. These antibodies can cross the placenta during subsequent pregnancies and attack the red blood cells of the second Rh-positive baby, leading to hemolysis and HDNB.

If the first baby is Rh-negative, the mother's immune system remains unsensitized. When the second baby is Rh-positive, this pregnancy serves as the sensitizing event, and the mother begins producing anti-Rh antibodies only after this exposure. Consequently, it is typically the third Rh-positive baby who faces the risk of HDNB, not the second.

Understanding the Rh factor and the timing of maternal sensitization is crucial in predicting and managing hemolytic disease of the newborn. This knowledge guides prenatal care, including the administration of Rh immunoglobulin to Rh-negative mothers to prevent sensitization and protect future pregnancies.

A mother is pregnant with her first child. The mother has Rh^— blood and the infant has Rh⁺ blood. What is likely to occur during pregnancy/birth?

• A. The mother is “sensitized” to the Rh antigen and eventually begins to create anti-Rh antibodies.
• B. The infant’s immune system immediately attacks the mother’s blood, resulting in a severe cytotoxic reaction.
• C. The infant’s Rh antigens will break down so that the infant’s blood type matches the mother’s blood type.
• D. If the mother is not given RhoGAM, her immune system will attack the infant’s RBCs, causing major damage.

Answer: (A)

Here’s what students ask on this topic:

What are Type II hypersensitivities and how do they differ from Type I hypersensitivities?

Type II hypersensitivities, also known as cytotoxic hypersensitivities, involve IgG or IgM antibodies targeting antigens on cell surfaces or in the extracellular matrix. Unlike Type I hypersensitivities, which are mediated by IgE antibodies and typically involve allergic reactions, Type II hypersensitivities cause direct cell damage or death. This occurs through mechanisms such as complement activation, antibody-dependent cellular cytotoxicity (ADCC), or inflammation, leading to tissue damage. These hypersensitivities can target foreign cells, like in blood transfusion reactions, or self cells, causing autoimmune disorders. The key difference is that Type II hypersensitivities involve cytotoxic effects mediated by IgG or IgM antibodies, whereas Type I hypersensitivities involve IgE antibodies and allergic responses.

How does the ABO blood group system affect blood transfusion compatibility?

The ABO blood group system classifies blood into four types based on the presence or absence of A and B carbohydrate antigens on red blood cells: Type A (A antigen), Type B (B antigen), Type AB (both A and B antigens), and Type O (neither antigen). Individuals naturally produce antibodies (isohemagglutinins) against the ABO antigens they lack. For example, Type A individuals produce anti-B antibodies. During blood transfusions, if the recipient's antibodies recognize donor red blood cell antigens as foreign, they bind and cause cell destruction, leading to hemolytic transfusion reactions. Therefore, transfusion compatibility depends on matching donor red blood cell antigens with recipient antibodies to avoid immune attack and ensure safety.

What role does the Rh blood system play in transfusion reactions and hemolytic disease of the newborn?

The Rh blood system involves the presence (Rh positive) or absence (Rh negative) of the Rh factor protein on red blood cells. Unlike ABO antibodies, anti-Rh antibodies are not naturally present but develop after exposure to Rh-positive blood in Rh-negative individuals. In transfusions, Rh-negative recipients can develop anti-Rh antibodies if given Rh-positive blood, risking hemolytic transfusion reactions. In pregnancy, an Rh-negative mother carrying an Rh-positive fetus can become sensitized to Rh antigens, producing anti-Rh antibodies that cross the placenta in subsequent pregnancies and destroy fetal red blood cells, causing hemolytic disease of the newborn (HDNB). This condition can lead to severe fetal complications but is preventable with treatments like RhoGAM.

What are the donate and receive rules for safe blood transfusions based on ABO and Rh blood types?

The donate and receive rules guide safe blood transfusions by considering red blood cell antigens. The Donate Rule states that a donor can give blood only to recipients whose red blood cells have at least the donor's antigens. For example, a person with A positive blood (A and Rh antigens) can donate to recipients with A positive or AB positive blood. The Receive Rule states that a recipient can receive blood only from donors whose red blood cells have at most the recipient's antigens. For instance, an A positive recipient can receive blood from A positive, A negative, O positive, or O negative donors. These rules prevent immune reactions by avoiding antibody-antigen mismatches. Notably, AB positive is the universal recipient, and O negative is the universal donor.

What causes hemolytic transfusion reactions and what are their consequences?

Hemolytic transfusion reactions (HTRs) are caused by a cytotoxic Type II hypersensitivity when a recipient receives incompatible donor red blood cells. The recipient's antibodies bind to foreign antigens on donor red blood cells, triggering their destruction through complement activation or ADCC. This leads to red blood cell lysis, releasing cell contents that cause inflammation, blood clotting, kidney damage, shock, and potentially organ failure. HTRs are serious and life-threatening, emphasizing the importance of matching blood types correctly during transfusions to prevent immune-mediated destruction of transfused cells.

How does hemolytic disease of the newborn (HDNB) develop and how can it be prevented?

Hemolytic disease of the newborn (HDNB) occurs when an Rh-negative mother becomes sensitized to Rh-positive fetal red blood cell antigens, usually during the birth of her first Rh-positive child. This sensitization leads the mother to produce anti-Rh IgG antibodies. In subsequent pregnancies with Rh-positive fetuses, these maternal antibodies cross the placenta and destroy fetal red blood cells, causing anemia, heart failure, jaundice, brain damage, or death. HDNB can be prevented by administering RhoGAM, a medication containing anti-Rh antibodies, to the mother during and after the first pregnancy. RhoGAM binds fetal Rh antigens in the mother's circulation, preventing her immune system from becoming sensitized and producing harmful antibodies, thereby protecting future pregnancies.